Molecular dynamics simulations indicate that deoxyhemoglobin,oxyhemoglobin, carboxyhemoglobin,and glycated hemoglobin under compression and shear exhibit an anisotropic mechanical behavior

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells, using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO₂), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA_1C). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.     

Hemoglobin autofluorescence as potential long-term glycemic marker in the rat animal model

Diabetes is a serious disease whose patients often require long-term care. Blood glucose and intermediate glycation product of glycated hemoglobin (HbA1c) are, at best, surrogate biomarkers of disease progression. There is indication that advanced glycation end products (AGEs) better reflect diabetic risks. In this study, we explored the use of red blood cells (RBCs) and lysed hemoglobin (Hb) autofluorescence (AF) as potential biomarkers of diabetic complication. AF spectra measured under 370 nm excitation reveals that both RBC and Hb fluorescence in the 420 to 600 nm region. At early time points following diabetic induction in rats, AF increase in lysed Hb is more dramatic compared to that of RBCs. Moreover, we found significance variance of Hb autofluorescence despite relatively constant HbA1c levels. Furthermore, we found that although a correlation exists between AGE autofluorescence and HbA1c levels, the lack of complete correspondence suggests that the rate of AGE production differs significantly among different rats. Our results suggest that with additional development, both RBC and Hb autofluorescence from lysed RBCs may be used act long-term glycemic markers for diabetic complications in patients.      

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.     

Optical coherence hyperspectral microscopy with a single supercontinuum light source

In the paper, we have developed an optical coherence hyperspectral microscopy with a single supercontinuum light source. The microscopy consists of optical coherence tomography (OCT) and hyperspectral imaging (HSI), which can visualize the structural and functional characteristics of biological tissues. The 500 to 700 nm band is selected for HSI and OCT imaging, where HSI enables imaging of oxygen saturation and hemoglobin (Hb) content, while OCT acquires structural characteristics to assess the morphology of biological tissues. The system performance of the optical coherence hyperspectral microscopy is verified by normal mice ears, and the practical applications of the microscopy is further performed in 4T1 and inflammation Balb/c mice ears in vivo. The experimental results demonstrate that the microscopy has potential to provide complementary information for clinical applications.     

Digital Health and Shared Decision-Making in Diabetes Care – A Survey Initiative in Patients and Clinicians

ObjectiveTo assess the landscape of digital health resources in the United States, better understand the impact of the digital health on shared decision-making, and identify potential barriers and opportunities for progress in the care of persons with diabetes.MethodsThe study consisted of two phases: A qualitative phase in which one-on-one interviews were conducted virtually with 34 physicians (endocrinologists {Endos}: n = 15; primary care physicians {PCPs}: n = 19) between February 11, 2021 and February 18, 2021, and a quantitative phase in which two online, email-based surveys in the English language were conducted between April 16, 2021 and May 17, 2021: one with healthcare professionals (HCP) (n = 403: n = 200 Endos and n = 203 PCPs), and one with persons with diabetes (n = 517: patients with type 1 diabetes, n = 257; patients with type 2 diabetes, n = 260).ResultsDiabetes digital health tools were found to be helpful in shared decision-making, but leading barriers include cost, coverage, and lack of time by healthcare professionals. Among diabetes digital health tools, continuous glucose monitoring (CGM) systems were used most commonly and viewed as most effective in improving quality of life and facilitating shared decision-making. Strategies for increasing use of diabetes digital health resources included lower cost, integration into electronic health records, and increased simplicity of tools.ConclusionThis study revealed that both Endos and PCPs feel that diabetes digital health tools have an overall positive impact. Integration with telemedicine and simpler, lower cost tools with increased patient access can further facilitate shared decision-making and improved diabetes care and quality of life.     

Development of a simple assay system for protein-stabilizing efficiency based on hemoglobin protection against denaturation and measurement of the cooperative effect of mixing protein stabilizers

We have elucidated the cooperative stabilization of proteins by sugars, amino acids, and other protein-stabilizing agents using a new and simple assay system. Our system determines the protein-stabilizing ability of various compounds by measuring their ability to protect hemoglobin from denaturation. Hemoglobin denaturation was readily measured by quantitative changes in its ultraviolet–visible absorption spectrum. The efficiency of our assay was confirmed using various sugars such as trehalose and sucrose that are known to be good protein stabilizers. We have also found that mixtures of two different types of protein stabilizers resulted in a cooperative stabilizing effect on protein.     

Hybrid Closed-Loop Insulin Pump Technology Can Be Safely Used in the Inpatient Setting

BackgroundHybrid closed-loop (HCL) systems, also known as automated insulin delivery systems, are a rapidly growing technology in diabetes management. Because more patients are using these systems in the outpatient setting, it is important to also assess inpatient safety to determine whether HCL use can be continued when those patients become hospitalized.MethodsThe records of patients using HCL technology on admission to our hospital between June 1, 2020, and June 30, 2021, were analyzed.ResultsThe final analysis included 71 patients divided into 3 categories based on their pump use as an inpatient: (1) HCL users; (2) manual pump users; and (3) pump removed. All cohorts were similar in age, sex, race, hemoglobin A1C at admission, and in Medicare Severity Diagnosis Related Group. Pairwise comparisons indicated that patient-stay mean glucose levels, frequency of patient-specific hyperglycemic measurements, and frequency of hypoglycemic events were similar between all groups. No adverse events, particularly occurrences of diabetic ketoacidosis, pump site complications or infection, or equipment malfunction, were reported.ConclusionThis preliminary case series review indicates that continued use of HCL technology in the hospital is safe. Moreover, glycemic control in HCL users was comparable with that in those using insulin pump with manual settings and those converted to basal-bolus insulin therapy.     

Frequent Monitoring of Blood Glucose Levels via a Remote Patient Monitoring System Helps Improve Glycemic Control

ObjectiveThis study aimed to evaluate the effectiveness of the Vivovitals diabetes platform in improving glycemic control and reducing hemoglobin A1c (HbA1c) levels in patients with uncontrolled type 2 diabetes mellitus by providing more accessible and direct patient care under the monitoring and oversight of their physician.MethodsThis 12-week, prospective, pragmatic, single-center, double-arm study assessed the impact of the Vivovitals diabetes platform on glycemic control in 78 adults aged ≥18 years with HbA1c levels of ≥7.5% (58 mmol/mol) at baseline. The participants were randomized into 2 groups. The control group received usual clinical care, whereas the intervention group was provided with a smartphone-linked telehealth application, a preconfigured glucometer, and access to a glycemic reading diary. The blood glucose levels of the intervention group were transmitted to the providers daily. Patients whose blood glucose level was <70 mg/dL or >180mg/dL were contacted, and modifications were made to their diet and medication. The 2 groups were compared at the baseline and at 12 weeks using nonparametric tests, with P <.05 considered statistically significant.ResultsOver 12 weeks, the average HbA1c level in the control group reduced by 0.474% (P = .533; 95% CI, −0.425 to −0.523), whereas the average HbA1c level in the intervention group reduced by 1.70% (P = .002; 95% CI, −1.02 to −2.39). The estimated treatment difference was expressed using Cohen d, which yielded 0.62. After 12 weeks, the HbA1c values between the control and intervention groups were statistically significant (P = .001).ConclusionThe use of the Vivovitals platform may help to improve glycemic control among individuals with type 2 diabetes mellitus.     

Conformational dynamics of the tetrameric hemoglobin molecule as revealed by hydrogen exchange: I. Effects of pH,temperature, and ligand binding

IR spectroscopy was used to study the rate of hydrogen-deuterium (H-D) exchange of peptide NH atoms in different forms of human hemoglobin (Hb) at pH 5–10 and temperatures of 10–63°C. The pH dependence of the H-D exchange rate fits the EX2 mechanism. At 10–30°C, there are two pH-dependent conformers of liganded Hb forms, the fluctuation probability being lower for the alkaline conformer. The differences between the conformers disappear at 40°C, where a third conformer, with a higher probability of local fluctuations, appears. Deoxyhemoglobin has no pH-dependent conformers in the pH range 6–9 at 20°C, and the probability of local fluctuations is considerably decreased compared to the acid conformer of liganded Hb. The destabilization of the liganded Hb structure by decreasing the pH to 5.0 at 20°C or increasing the temperature to 50–60°C at pH 7.1 enhances global fluctuations of the native structure ensuring the H-D exchange of slowly exchanging NH atoms. The mechanisms of local and high-temperature global fluctuations, as well as the possible similarity between the two pH-dependent conformers of liganded Hb and its functional R and R2 states revealed by X-ray analysis and NMR spectroscopy, are discussed.     

Mechanisms involved in proteolytic degradation of globular proteins: The role of local and global fluctuations in the native structure

The mechanisms involved in degradation of the native protein structure was analyzed by comparing the temperature dependences of the hydrogen exchange (HE) and proteolytic cleavage rates of hen egg lysozyme (HEL), human hemoglobin (Hb), and its apoform (apoHb). Acceleration of the burstlike (all or none) proteolytic degradation of HEL in a high temperature range results from the intensification of global fluctuations with overal structure unfolding, indicated by HE. The rates of Hb and apoHb burstlike degradation and HE weakly depend on the temperature in the range where only local fluctuations of the native structure are detectable by HE. These two proteins are cleaved according to a self-accelerated burstlike mechanism with the initial rate-limiting single cleavage due to local fluctuations in the native structure. Such fluctuations play an important role in intracellular burstlike proteolytic degradation of native proteins.